Prostate cancer (PC) screening using prostate-specific antigen (PSA) testing with systematic biopsy (SBx) reduces mortality but risks overdiagnosis and unnecessary biopsies. Multiparametric MRI (mpMRI) enables MRI-targeted biopsy (TBx) of suspicious lesions and is now recommended before biopsy, although its role in primary screening, particularly in younger men, remains uncertain due to interpretive challenges. The PROBASE trial is a prospective randomised screening study enrolling 46,495 men aged 45 years. Participants with PSA ≥3ng/ml underwent mpMRI, followed by both SBx and TBx. This analysis included 525 men biopsied between 2014 and 2023. The primary endpoint was detection of clinically significant PC (csPC; ISUP grade group ≥2). Of 525 participants, 209 PCs were detected (39%), with 148 (71%) being csPC. SBx identified 94% of csPC versus 74% for TBx (p<0.05). SBx detected 26% of csPC cases missed by TBx, while TBx detected 6% missed by SBx. For ISUP 1 cancers, SBx also outperformed TBx (84% vs. 43%; p<0.001). MRI detected 91% of csPC, but 14 csPC cases were MRI-invisible. Thus, omitting SBx would have missed one-quarter of csPC diagnoses. SBx performed particularly well in younger men, likely owing to smaller prostate volumes allowing better systematic sampling. Missed SBx cases were mainly due to anterior or apical tumour locations. MRI interpretation in this cohort was challenging, with a high proportion of equivocal PI-RADS 3 lesions. While MRI-TBx reduces overdiagnosis, only 29% of detected cancers were ISUP 1, suggesting limited overtreatment risk compared with older cohorts. Limitations include MRI performed only for elevated PSA, variability in MRI quality and biopsy technique, and modest sample size. In conclusion, SBx remains essential in younger men, with combined SBx+TBx providing the most accurate PC detection. Future work should refine MRI interpretation, incorporate AI, and optimise biopsy strategies to enhance early detection while minimising overtreatment.
Prostate cancer detection in younger men
Reviewed by Asif H Ansari
Prostate cancer detection in younger men: a comparative analysis of systematic and magnetic resonance imaging–targeted biopsy in the PROBASE trial.
